The study is now published online in Scientific Reports, a journal from the Nature Publishing Group.
Liggins Institute molecular biologist, Dr Justin O'Sullivan, says the findings on how crowded genes behave are important for our understanding of development and disease.
The researchers developed 3D digital models of how the DNA is folded inside the nucleus of a yeast cell, and then mapped how genes encoded in the DNA are clustered inside the nucleus.
They found that the regions of DNA that control replication are crowded together. By mutating certain genes they could change the pattern of crowding and thus the timing of replication.
They also found that those genes that were turned on – or expressed – were physically separated from those that were turned off.
"The more we understand about what's happening to the genes encoded in the DNA inside the cell nucleus, the easier it is to understand how that DNA structure responds to the environment outside the cell," Dr O'Sullivan says.
"So these findings add to our understanding of epigenetics - the chemical process in which the environment modifies the DNA, switching the genes responsible for certain developmental processes on or off.
"Our next step is to investigate whether the development of common diseases is influenced by the way genes with mutations are crowded together and communicate with one another," he says.
The researchers used a 3D digital model to examine the folding of the DNA inside the yeast cell nucleus. They verified the model using measurements from live yeast cells.
Explore further: Mapping the 3-D structure of DNA
More information: T. Pichugina et al. A diffusion model for the coordination of DNA replication in Schizosaccharomyces pombe, Scientific Reports (2016). DOI: 10.1038/srep18757

Miller C.A.,Washington University in St. Louis | White B.S.,Washington University in St. Louis | White B.S.,University of Washington | Dees N.D.,Washington University in St. Louis | And 21 more authors.PLoS Computational Biology | Year: 2014

Background The recently published INTERGROWTH-21st Project international population standard for newborn size is intended for global use, but its ability to identify small infants at risk of adverse outcomes in a general obstetric population has not been reported. Objective The objective of the study was to compare adverse neonatal outcomes among small-for-gestational-age (SGA) infants between the INTERGROWTH-21st standard and a customized birthweight standard (accounting for maternal characteristics of height, weight, parity, and ethnicity). We hypothesized that in a multiethnic general obstetric population in Auckland, New Zealand, a customized birthweight standard would better identify SGA infants at-risk of neonatal morbidity/mortality and stillbirth than the INTERGROWTH-21st standard. Study Design Using prospectively gathered maternity data from a general obstetric population in Auckland, New Zealand, from 2006 to 2013 (n = 53,484 births at ≥ 33 weeks), infants were classified as SGA (birthweight < 10th centile) by INTERGROWTH-21st and customized standards. Infants were further categorized as SGA by both criteria, INTERGROWTH-21st only, customized only, or not SGA (met neither criteria). Composite adverse neonatal outcome was defined as neonatal death, neonatal intensive care admission > 48 hours, or ventilation > 4 hours or 5-minute Apgar score < 7. Relative risks for primary outcomes were estimated using modified Poisson regression, with the non-SGA group as the referent. Results Incidence of SGA was 4.5% by INTERGROWTH-21st and 11.6% by customized standard. Compared with those not SGA, infants identified as small for gestational age by both criteria had the highest risk of adverse neonatal outcome (relative risk [RR], 4.1, 95% confidence interval [CI], 3.7-4.6) and stillbirth (RR, 8.3, 95% CI, 5.1-13.4). Infants SGA by customized standard only (n = 4015) had an increased risk of adverse neonatal outcome (RR, 2.0, 95% CI, 1.8-2.2) and stillbirth (RR, 3.0, 95% CI, 1.7-5.3). Few infants were identified as SGA by INTERGROWTH-21st only (n = 172), and risks of adverse neonatal outcome and stillbirth were not increased. Findings were unchanged when analyses were limited to term infants (n = 50,739). The INTERGROWTH-21st standard identified more Indian (12.8%) and Asian (5.8%) but fewer European (3.0%) and Pacific (2.9%) infants as SGA (P Source